Modulation of ATP-sensitive K+ channels in rabbit ventricular myocytes by adenosine A1 receptor activation
Kim, E.; Han, J.; Ho, W.; Earm, Y.E.
American Journal of Physiology 272(1 Pt 2): H325-H333
1997
ISSN/ISBN: 0002-9513 PMID: 9038953 Document Number: 471241
The objective of the present study was to characterize the role of adenosine in the regulation of ATP-sensitive K+ (K-ATP) channel activity in isolated rabbit ventricular myocytes using the patch-clamp technique. In an outside-out patch exposed to guanosine 5'-triphosphate and ATP at the intracellular surface, external adenosine stimulated K-ATP channel activity. In an inside-out patch exposed to external adenosine, ATP reduced K-ATP channel activity and guanosine 5'-triphosphate stimulated K-ATP channel activity. Guanosine 5'-O-(3-thiotriphosphate) resulted in a gradual increase of K-ATP channel activity even in the absence of adenosine. When myocytes were preincubated with pertussis toxin or 8-cyclopentyl-1,3-dipropylxanthine, adenosine A-1 receptor activation failed to activate the K-ATP channel. Analysis of the open and closed time distributions showed that adenosine A-1 receptor activation increased burst duration and decreased interburst duration. In a dose-response relationship for ATP, adenosine A-1 receptor activation shifted the half-maximal inhibition of the K-ATP channel from 70 to 241 mu-M.